Title : Blocking von Willebrand factor free thiols inhibits binding to collagen under high and pathological shear stress.

Pub. Date : 2021 Feb

PMID : 33075181






15 Functional Relationships(s)
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1 Blocking Von Willebrand Factor Free-Thiols inhibits binding to collagen under high and pathological shear stress. Sulfhydryl Compounds von Willebrand factor Homo sapiens
2 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
3 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
4 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
5 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
6 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
7 BACKGROUND: Von Willebrand Factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free-thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Sulfhydryl Compounds von Willebrand factor Homo sapiens
8 RESULTS: Blockade of VWF free-thiols reduced VWF mediated platelet capture to collagen in a shear dependent manner, with platelet capture virtually abolished above 5000s-1 and in regions of stenosis in microfluidic channels. Sulfhydryl Compounds von Willebrand factor Homo sapiens
9 RESULTS: Blockade of VWF free-thiols reduced VWF mediated platelet capture to collagen in a shear dependent manner, with platelet capture virtually abolished above 5000s-1 and in regions of stenosis in microfluidic channels. Sulfhydryl Compounds von Willebrand factor Homo sapiens
10 AFM measurements showed that thiol-blockade reduced the life-time and strength of the VWF-collagen bond. Sulfhydryl Compounds von Willebrand factor Homo sapiens
11 Pulling simulations of the VWF-C4 domain demonstrated that with one or two reduced disulphide bonds the C4 domain has increased flexibility and the propensity to undergo free-thiol exchange. Sulfhydryl Compounds von Willebrand factor Homo sapiens
12 CONCLUSIONS: We conclude that free-thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognised role for VWF free-thiols. Sulfhydryl Compounds von Willebrand factor Homo sapiens
13 CONCLUSIONS: We conclude that free-thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognised role for VWF free-thiols. Sulfhydryl Compounds von Willebrand factor Homo sapiens
14 CONCLUSIONS: We conclude that free-thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognised role for VWF free-thiols. Sulfhydryl Compounds von Willebrand factor Homo sapiens
15 CONCLUSIONS: We conclude that free-thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognised role for VWF free-thiols. Sulfhydryl Compounds von Willebrand factor Homo sapiens